This plan proposes to investigate the molecular pathogenesis of FIV infection in cats. Information from these studies will be used to obtain a better understanding of the molecular pathogenesis of HIV infection. Analysis of the molecular pathogenesis of FIV infection will involve molecular cloning and comparative sequence analysis of proviral DNAs from a number of FIV isolates. We will also study the nature of control of viral gene expression in a number of cell types. Isolation of replication competent and defective proviruses directly from the tissues of naturally infected cats will be accomplished by molecular cloning. They will be analyzed by restriction endonuclease mapping and sequence analysis. Further analysis in vitro and in vivo for cytopathic effect, infectivity, latency, and target cell will be performed using existing antigen assays and monoclonal antibodies in combination with flow cytometry, polymerase chain reaction (PCR),amplification of viral sequences and tests for immune function. Monoclonal antibodies specific for feline lymphocyte cell types will also be developed, and used to perform detailed analysis of the feline immune system in FIV infected and uninfected cats. Utilization of these reagents will allow a better understanding of FIV pathogenesis in SPF cats, as well as cats infected with other feline pathogens.